This application for a SPORE in breast cancer represents a collaboration between the University of California at San Francisco (UCSF) and the California Pacific Medical Center (CPMC). The proposal places a high priority on translational research both in the specific projects described and in proposals for future projects utilizing developmental research and career development funds. Projects have been identified which place considerable emphasis on increasing our understanding of the events which lead up to invasion and metastases and on the development of strategies to prevent the disease or intervene very early in the disease process. In general the proposal has avoided studies using conventional modes of treatment, including high dose chemotherapy and endocrine therapy, since studies of these modalities are better conducted within the context of the cooperative groups. The SPORE application has been built in collaboration with a successful program project grant for breast cancer, and while personnel and resources of the two will be shared, thus strengthening each program, considerable effort has been taken to design projects which do not overlap with those in the program project. One of the most important and central of the proposed Core resources is a tumor tissue bank which will represent a substantial expansion of a project begun very successfully by the program project but which has not been able to grow beyond Moffitt-Long at UCSF because of a lack of funds for technical support in other hospitals. The strengths of UCSF and the Bay Area in general have been emphasized, including the many excellent molecular biology and molecular genetics laboratories, the large and well organized breast screening programs, and the biotechnology industry in the Bay Area which is likely to prove important in the translational aspects of this SPORE. Collaborations have been developed outside of San Francisco to include the human genome project at Los Alamos and the pathology department at the Massachusetts General Hospital in Boston. It is hoped that a SPORE award will also strengthen areas relatively underdeveloped in the Bay Area and will contribute to the development of a cooperative effort in the conduct of clinical trials and the management of women at high risk of developing breast cancer. this application consists of four research projects, four core resources, and a section on developmental research and career development. The four projects are: #1 The development of tumoricidal, membrane receptor targeted, breast cancer therapy; #2 Analysis of gene deletion and amplification in human breast cancer; #3 Molecular markers defining groups of women at unusually high risk of developing breast cancer; #4 Therapeutic Blockade of the Urokinase Receptor. The four cores are: #1 Human fresh tissue bank; #2 An animal facility; #3 Epidemiology and biostatistics; #4 Clinical core. Each project has developed a distinct plan for clinical application, and it is anticipated that each will begin (and in some cases) complete a clinical protocol growing out the project within the three years of the grant.